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PDAT3 > 16/17/18 - Diuretics > Flashcards

16/17/18 - Diuretics Flashcards

1
Q

Which DIURETIC?

A
  • *BUMETANIDE**
  • *LOOP DIURETIC**

40-50x more potent than furosemide

Sulfonamide moiety
in furosemide and bumetanide also
provides weak CA inhibitory activity, thus
increase phosphate and bicarbonate excretion.

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2
Q

Which Diuretic causes this side effect?

“Contraction” Alkalosis

A

LOOP DIURETICS
Furosemide, Bumetanide, Torsemide, Ethacrinic Acid

Due to:
Significant diuresis can lead to hypovolemia ‐> stimulation of Aldosterone ‐> H+ excretion

Also:
HypoCalcemia*** // ***HypoMagnesemia
Ototoxicity // GOUT
Mild - HYPERglycemia / increase in Cholesterol / TG’s

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3
Q

Edema Treatment

A

Mainstay of therapy is:
NaCl RESTRICTION
diuretics will NOT work if the increased loss is REPLACED by MORE NACL INTAKE
Restriction depends on degree of edema:
SEVERE EDEMA: <1gm NaCl per day

  • *Loop Diuretics are 1st line after**
  • *daily dosing** –> increase dose or BID
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4
Q

Which DIURETIC?

A

Dichlorfenamide​
META-disulfamoylbenzene derivatives

Carbonic Anhydrase Inhibitor

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5
Q

Which DIURETIC?

A
  • *FUROSEMIDE**
  • *LOOP DIURETIC**

Sulfonamide moiety
in furosemide and bumetanide also
provides weak CA inhibitory activity, thus
increase phosphate and bicarbonate excretion.

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6
Q

Which Diuretic?

A
  • *Acetazolamide**
  • *SIMPLE heterocyclic sulfonamides**

Carbonic Anhydrase Inhibitor

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7
Q

Which Diuretic causes this side effect?

METABOLIC ACIDOSIS

A

CAIs
Acetazolamide + Methazolamide (Simple)
Dichlorfenamide + Dorzolamide (meta)

HCO3 is indirectly REABSORBED by CA
VVV
Blocking CA –> less HCO3 reabsorbed // more EXCRETED
VVV
METABOLIC ACIDOSIS

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8
Q

Which Diuretic causes this side effect?

HypoCalcemia

A

LOOP DIURETICS
•Furosemide, Bumetanide, Torsemide, Ethacrinic Acid

Also:
HypoKalemia // HypoMagnesemia
Ototoxicity // GOUT // Contaction ALKAlosis
Mild - HYPERglycemia / increase in Cholesterol / TG’s

Also used for:
Severe HYPERcalcemia
but MAINLY EDEMA
not proven to be good for HYPERtension

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9
Q

Which Diuretic causes this side effect?

HypoNatremia

A

THIAZIDE DIURETICS

Also:
HYPERcalcemia
HypoKalemia*** / ***HypoMagnesemia / GOUT
and MILD:
HyperGlycemia // TG // Cholesterol

INEFFECTIVE @ CrCl <30 mL/min
need RENAL function

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10
Q

What occurs in the ASCENDING LIMB?

Urine Formation

A
  • *“Dilution of Luminal Fluid”**
  • water IMpermeable*

RE-absorption of NaCl
30% of filtered Na+ –> reenters

Para-cellular Transport
used to compensate for HIGH Na+

  • *Symporter_ + _Antiporter**
  • *ATPase**
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11
Q

Which Diuretic is indicated for:
DECREASED MORTALITY**in**HFrEF
heart failure w/ reduced ejection fraction

A

Aldosterone Antagonist
Spironolactone & Eplerenone
K+ sparing Diuretics, weak diuretic

Other indications:
Combo w/ HCTZ to prevent hypokalemia

Hepatic Cirrhosis w/ ascites

Resistant Hypertension

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12
Q

2-Step Concentration Process
of
Renal Tubular Secretion
(1 of 2 ways to enter into the luminal fluid, Glomerular Filtration is the other)

A

@PROXIMAL TUBULE

1) Active Secretion, interstitium –> proximal tubule
via OATS / OCTS
most diuretics are either weak organic acids or weak organic bases
important for GOUT –> URIC ACID competes with DIURETICS

2) Passive + Active Transport, Proximal Tubule –> Luminal Fluid
of diuretics

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13
Q

Which DIURETIC?

A

SORBITOL

Osmotic Diuretic

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14
Q

Which DIURETIC, based on MECHANISM OF ACTION?

  • Inhibition of*
  • *Renal Carbonic Anhydrase**
  • decreases the:*
  • *Sodium Carbonate Reabsorption**
A

Carbonic Anhydrase Inhibitors
CAI

Acetazolamide + Methazolamide
(Simple)
&
Dichlorfenamide + Dorzolamide
(meta)

Act on:
Proximal Tubule

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15
Q

Which DIURETIC?

A

MANNITOL
Isomer of SORBITOL

Osmotic Diuretics

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16
Q

Which DIURETIC?

A
  • *TORSEMIDE**
  • *Loop Diuretic**
  • *sulfonylurea lacking an unsubstituted sulfamoyl group,**
  • does not act at the proximal tubule*
  • therefore does NOT increase phosphate or bicarbonate excretion.*

= no CA activity

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17
Q

Which Diuretic causes this side effect?

HYPERkalemia

A

K+ Sparing Diuretics

–Requires regular monitoring – can cause fatal arrhythmias
Risk increases greatly with CrCl < 50
Discontinue if K > 5.0 or CrCl < 30
Use in patients on dialysis is controversial in patients with HFrEF

Spironololactone also:
GYNECOMASTIA

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18
Q

What occurs in the COLLECTING DUCT?

Urine Formation

A

Re-Absorption of Water

  • *Reabsorption & Secretion of**
  • *Na / K / H / HCO3**

Na+/K+ ATPase
driving force for re-absprotion

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19
Q
  • *What conditions cause a
  • Diminished response to LOOP DIURETICS?***
A

Renal Insufficiency / Nephrotic Syndrome

Heart Failure / Cirrhosis

  • may require
  • HIGHER DOSES –> reach ceiling/max effect**

Ceiling dose:

  • *80-160mg** for Furosemide
  • *1-2 mg** for Bumetanide
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20
Q

How does the nephron REACT to HYPOVOLEMIA?

Reduced Plasma Volume or Dehydration

A

↓Renal Blood flow
↓GFR

↑Renin Secretion

↑Antidiuretic Hormone
increase in water RE-absorption

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21
Q

Which DIURETIC?

A
  • *ETHCRYNIC ACID_ + _INDACRINONE**
  • *Phenoxyacetic Acid-type High Ceiling Diuretics**

In addition to inhibit ATPase;
it also blocks the luminal Na+/K+/2Cl- co- transporter similar to furosemide

no sulfonamide group = does NOT inhibit CAI

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22
Q

Which DIURETIC?

A
  • *EPLERENONE**
  • *K+ Sparing Diuretic**

Aldosterone Receptor Agonist

Eplerenone, a newer aldosterone receptor antagonist with better ADH receptor selectivity than spironolactone.

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23
Q

What can NOT be taken with a LOOP DIURETIC?

A

THIAZIDE DIURETICS

CAN NOT BE TAKEN WITH LOOP DIURETICS

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24
Q

What group on Thiazide Diuretics is associated with:

HyperSensitivity Rxns / Drug-Induced Fever

Blood Dyscrasias / Interstitial Nephritis

Cross Sensitivity with CAI’s
+ loop diuretics or antibiotics with this group

A

SULFAMOYL MOIETY
SO2NH2

Thiazide Diuretics also have ADR of:
HypoKalemia

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25
**Which DIURETIC acts on:** **EARLY DISTAL TUBULE**
**_THIAZIDE DIURETICS_**
26
**Which DIURETIC acts on:** **THICK ASCENDING LIMB**
**_LOOP DIURETICS_** Furosemide / Bumetanide / Torsemide
27
Which DIURETIC, based on MECHANISM OF ACTION? ***Sodium and water reabsorption decreases*** because of ***reduced medullary hyper tonicity*** and **elevated urinary flow rate**
**OSMOTIC DIURETIC** **Mannitol / Isosorbide / Sorbitol** Act on: **Proximal Tubule** & **Descending Limb**
28
**Indication for these K+ Sparing Diuretics:** **Sodium Channel Blockers** (of Collecting Ducts) **Triamterene / Amiloride**
***_very weak diuretics_*** Often used in: **COMBO with HCTZ** to ***_PREVENT HypoKalemia_***
29
Which DIURETIC, based on MECHANISM OF ACTION? * **INHIBITION OF*** * *Na+ - Cl- Symporter**
**_THIAZIDES_** + *Thiazide -like* **All Thiazides also have _CA inhibition_!** Act at the: beginning of the **DISTAL TUBULE**
30
**Which DIURETIC?**
* *_Dorzolamide_** * *META-disulfamoylbenzene derivatives** ## Footnote **Carbonic Anhydrase Inhibitor**
31
**_Benzothiazide (Thiazide) Diuretics_** **Which is ESSENTIAL FOR DIURETIC ACTIVITY?**
**_Sulfonamide**_ @ _**C-7_** is essential for diuretic Activity **_EWG**_ @ _**C-6_** is needed for diuretic activity
32
**_Benzothiazide (Thiazide) Diuretics_** **What can only TOLERATE a METHYL GROUP?** & **What can be REPLACED?** Carbonyl containing groups can replace the sulfonamide group at S-1 and N-2.
**_N-2_** can only tolerate a **methyl group** *will stop the THIAZIDE DIURETIC effect, but not CAI* **_Carbonyl-containing groups**_ --\> _**Sulfonamide_** at **_S-1**_ & _**N-2_** can replace sulfonamide with no problem
33
**Which DIURETIC?**
* *_AMILORIDE_** * *K+ Sparing Diuretic** **SELECTIVE SODIUM CHANNEL BLOCKER** **Highly Basic** amiloride is **excreted unchanged** since ***it is not further metabolized***
34
**How do Thiazide Diurteics / Loop Diuretics** **cause** **HypoKalemia**?
In the **_Collecting Duct_:** **Increased Na+ Concentration in Urine** VV **Increased K+ Secretion into Urine** VVV **K+ Is released with the urine** **"Na+ back IN --\> K+ OUT**"
35
**Which DIURETIC acts on:** **LATE DISTAL TUBULE** **+ COLLECTING DUCT**
**_POTASSIUM SPARING DIURETICS_** **SPIRONOLACTONE** Aldosterone / Canrenone / Eplerenone **TRIAMTERENE & AMILORIDE**
36
**What occurs in the: PROXIMAL TUBULE**? Urine Formation
**_REABSORPTION_** --\> into blood Glucose / Vitamins / AA / NaCl / HC03 / K / WATER * *_Transcellular Re-Absorption_** _by **CA** (carbonanhydrase)_ * *_Na+ / HCO3_** * passive processes:* * *_Transcellular Transport of_** * *Na+** coupled to **Glucose / AA / Phosphate** * *_PARAcellular Transport of_** * *Na+ / Cl-** * through the INTERcellular space*
37
**Causes of Edema**
**Increased Capillary Hydraulic Pressure** due to liver or heart failure ***_HypoALBUMINemia_*** due to nephrotic syndrome / malnutrition **Increased Capillary Permeability** due to massive INFLAMMATORY states = burn patients **Lymphedema** lymphatic obstruction
38
**Which DIURETIC?**
**_SPIRONOLACTONE_** --\> **Canerone** Canerone = **major active metabolite** **K+ Sparing Diuretic** **ALDOSTERONE RECEPTOR AGONIST** synthetic steroid that **blocks aldosterone receptors --\>** *less Na+/K+ ATPase* in **the later distal tubule** and **collecting duct**
39
**Indication for: OSMOTIC DIURETICS**
**_ELEVATED INTRACRANIAL PRESSURE_** * *Given IV** * **does NOT penetrate BBB*** Once filtered, *cannot be reabsorbed --\> pulls fluid into tubules for excretion*
40
**Which Diuretic is Indicated for:** **Prophylaxis of ACUTE ALTITUDE SICKNESS?**
**_CAIs_** Acetazolamide + Methazolamide (Simple) Dichlorfenamide + Dorzolamide (meta) ## Footnote **Also for: _GLAUCOMA_**
41
**Which Diuretic causes this side effect?** **HYPERcalcemia**
**_THIAZIDE DIURETICS_** Also: ***_HypoNatremia_*** ***_HypoKalemia***_ / _***HypoMagnesemia_*** / **GOUT** and MILD: **HyperGlycemia // TG // Cholesterol** ***INEFFECTIVE @*** **CrCl \<30 mL/min** need RENAL function
42
**Which Loop Diuretic** **does NOT have CA inhibitory Activity?**
**_TORSEMIDE_** ***does NOT have a* _Sulfonamide Moiety_** * does NOT increase * *_Phos // Bicarb excretion_*** Furosemide / Bumetanide does
43
**Phenoxyacetic Acid-Type High Ceiling Diuretics** MoA / Target
**_Etacrynic Acid**_ + _**Indacrinone_** Target: **Thick Ascending Limb** ***_Inhibits BOTH:_* ATPase** **Luminal Na/K/Cl- Co-Transporter** (similar to furosemide)
44
**Which Diuretic causes this side effect?** **_GOUT_**
**_LOOP DIURETICS_** Furosemide, Bumetanide, Torsemide, Ethacrinic Acid **_THIAZIDE DIURETICS_** Compete for elmination with: **_OATs_** VVV **ACCUMULATION OF _URIC ACID_**
45
**Which DIURETIC?**
**_Benzothiazide (Thiazide) Diuretics_**
46
**What occurs in the DISTAL TUBULE?** Urine Formation
* *Secretion: Ammonia / Uric Acid / Penicillin** * some WATER RE-absorption* **_Symporter_** Reabsorption of **NaCl --\>** epithelium **_Na+/ K+ ATPase_** driving force for **Re-absorption of Na --**\> Blood
47
**Which Diuretic?** Indication: **Mainly as ANTI-HYPERTENSIVE**, *not as diuretic* CI: ***INEFFECTIVE @* CrCl \< 30 mL/min**
**_Thiazide Diuretics_** HCTZ / Chlorthalidone Metolazone / Indapamide Cause: *HypoNatremia* *HypoKalemia* // *HypoMag* HYPERcalcemia / HYPERuricemia
48
Which DIURETIC, based on MECHANISM OF ACTION? ***Inhibition of Na+ & Water RE-absorption by:*** * *_Competitive Inhibition of Aldosterone Receptor_** * *"MineralCorticoid Receptor"**
**_POTASSIUM SPARING DIURETIC_** **_SPIRONOLACTIONE_** Aldosterone / Canrenone / Eplerenone Act on: late **DISTAL TUBULE** + **COLLECTING DUCT**
49
**_Benzothiazide (Thiazide) Diuretics_** * *What will:** * *increase diuretic potency** and/or i**ts duration of action?** * *What will: * diminishes diuretic activity?***
Substitution with a: **_LIPOPHYLIC GROUP**_ @ _**C-3_** INCREASES diuretic potency +/- Duration of action * any substitution of:* * *_Methyl Group**_ @ _**N-4**_ / _**C-5**_ / _**C-8_** * will DIMINISH diuretic activity*
50
**ADRs of Thiazides** HCTZ / Chlorthalidone Metolazone / Indapamide
* **_HYPO_*** * *K / Na** / **Mg** **_HYPER_** **Calcium** / **Uricemia (Gout) Glycemia / Cholesterol / LDL**
51
**What is Essential for CAI's Inhibitory Activity** SAR?
* *_UNSUBSTITUTED SULFAMOYL GROUP_** * *(SO2NH2)** +attached to a+ **_Aromatic**_ or _**Heterocyclic Ring_**
52
Which DIURETIC, based on MECHANISM OF ACTION? ***inhibition of the:*** **_Luminal Na+ / K+ / 2Cl- Transporter System_**
``` **_LOOP_** or **High- Ceiling** MOST POTENT class of diuretics ``` **Furosemide / Bumetanide / Torsemide** Act on: **THICK ASCENDING LIM****B**
53
**_methylxanthines_** **Diuretic** effect is due to **ability to increase renal blood flow** and **glomerular filtration rate**. •**Theophylline is most effective**
54
Which DIURETIC acts on: ## Footnote **PROXIMAL TUBULE**
**_CARBONIC ANHYDRASE INHIBITORS_** Acetazolamide + Methazolamide (Simple) Dichlorfenamide + Dorzolamide (meta) **_OSMOTIC DIURETICS_** Mannitol / Isosorbide / Sorbitol *also act on the DESCENDING LOOP*
55
Which DIURETIC, based on MECHANISM OF ACTION? ## Footnote ***Inhibition of Na+ & Water RE-absorption by:*** **_Blockade of Na+ Channel @ Luminal Membrane_**
**_POTASSIUM SPARING DIURETIC_** **_TRIAMTERENE & AMILORIDE_** Act on: **Late DISTAL TUBULE** & **COLLECTING DUCT**
56
**Which Diuretic?** **MoA: Compete with WATER + CO2** for binding in the same active site **Of the Target Enzyme**
* *_CAI's_** * *Carbonic Anhydrase** **Acetazolamide + Methazolamide** (Simple) & **Dichlorfenamide + Dorzolamide** (meta) Act on: Proximal Tubule
57
**What occurs in the DESCENDING LIMB?** Urine Formation
**"Concentration of Luminal Fluid" Osmotic Water Diffusion + Salts** (active) * *_WATER PERMEABLE_** * water is RE-ABSORBED here* **_Small amount of Na is ABSORBED_** active transport --\> into URINE
58
**Management of REFRACTORY EDEMA**
**_ASSURE COMPIANCE_** with **Diuretic & NaCl Restriction** **\<1gm NaCl / day** * _if ALL FAILS:_* * *Add Thiazide Diuretic** * CAUTION --\> PROFOUND DIURESIS / severe e- / volume depletion* * only for SEVERE cases*
59
**Which DIURETIC?**
**_Benzothiazide (Thiazide) Diuretics_** The differences in **_duration of action_** are dictated mainly due to the **_C-3_ substituent.​**
60
**Which DIURETIC?**
* *_TRIAMTERENE_** * *K+ Sparing Diuretic** **SELECTIVE SODIUM CHANNEL BLOCKER** **Highly Basic** Triamterene **metabolizes extensively by the liver enzymes** (due to the presence of the **phenyl ring**)
61
**Which DIURETIC?**
**_Methazolamide_ SIMPLE heterocyclic sulfonamides** **Carbonic Anhydrase Inhibitor**
62
**What Diuretic** **is the only one that DOES NOT ENTER THE TUBULAR LUMEN?**
**_Aldosterone Antagonist_** **Spironolactone / Eplerenone** K+ Sparing Diuretic ***Inhibit of the PRODUCTION of Na channels VVV*** ***reduce Na Reabsorption***
63
**Which diuretic has been shown to:** high quality of evidence for **_reducing morbidity and mortality for hypertension_** *but is the least used*
**_CHLORTHALIDONE_** **Thiazide Diuretic** HCTZ is still used the most **Metolazone and Indapamide** are generally only **used with Loop Diuretics for synergy**

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